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. 2023 Feb 1;6(2):e231181.
doi: 10.1001/jamanetworkopen.2023.1181.

Acute and Postacute COVID-19 Outcomes Among Immunologically Naive Adults During Delta vs Omicron Waves

Margaret K Doll  1 , Alpana Waghmare  2   3 , Antje Heit  4 , Brianna Levenson Shakoor  5 , Louise E Kimball  3 , Nina Ozbek  3 , Rachel L Blazevic  3 , Larry Mose  3 , Jim Boonyaratanakornkit  3 , Terry L Stevens-Ayers  3 , Kevin Cornell  6 , Benjamin D Sheppard  6 , Emma Hampson  6 , Faria Sharmin  1 , Benjamin Goodwin  5 , Jennifer M Dan  5   7 , Tom Archie  6 , Terry O'Connor  6   8 , David Heckerman  4 , Frank Schmitz  4 , Michael Boeckh  3   9 , Shane Crotty  5   7
Affiliations

Acute and Postacute COVID-19 Outcomes Among Immunologically Naive Adults During Delta vs Omicron Waves

Margaret K Doll et al. JAMA Netw Open. .

Abstract

Importance: The US arrival of the Omicron variant led to a rapid increase in SARS-CoV-2 infections. While numerous studies report characteristics of Omicron infections among vaccinated individuals or persons with previous infection, comprehensive data describing infections among adults who are immunologically naive are lacking.

Objectives: To examine COVID-19 acute and postacute clinical outcomes among a well-characterized cohort of unvaccinated and previously uninfected adults who contracted SARS-CoV-2 during the Omicron (BA.1/BA.2) surge, and to compare outcomes with infections that occurred during the Delta wave.

Design, setting, and participants: This prospective multisite cohort study included community-dwelling adults undergoing high-resolution symptom and virologic monitoring in 8 US states between June 2021 and September 2022. Unvaccinated adults aged 30 to less than 65 years without an immunological history of SARS-CoV-2 who were at high risk of infection were recruited. Participants were followed for up to 48 weeks, submitting regular COVID-19 symptom surveys and nasal swabs for SARS-CoV-2 polymerase chain reaction (PCR) testing. Data were analyzed from May to October 2022.

Exposures: Omicron (BA.1/BA.2 lineages) vs Delta SARS-CoV-2 infection, defined as a positive PCR test result that occurred during a period when the variant represented at least 50% of circulating SARS-CoV-2 variants in the participant's geographic region.

Main outcomes and measure(s): The main outcomes examined were the prevalence and severity of acute (≤28 days after onset) and postacute (≥5 weeks after onset) symptoms.

Results: Among 274 participants who were immunologically naive (mean [SD] age, 49 [9.7] years; 186 [68%] female; 19 [7%] Hispanic participants; 242 [88%] White participants), 166 (61%) contracted SARS-CoV-2. Of these, 137 infections (83%) occurred during the Omicron-predominant period and 29 infections (17%) occurred during the Delta-predominant period. Asymptomatic infections occurred among 7% (95% CI, 3%-12%) of Omicron-wave infections and 0% (95% CI, 0%-12%) of Delta-wave infections. Health care use among individuals with Omicron-wave infections was 79% (95% CI, 43%-92%) lower relative to individuals with Delta-wave infections (P = .001). Compared with individuals infected during the Delta wave, individuals infected during the Omicron wave also experienced a 56% (95% CI, 26%-74%, P = .004) relative reduction in the risk of postacute symptoms and a 79% (95% CI, 54%-91%, P < .001) relative reduction in the rate of postacute symptoms.

Conclusions and relevance: These findings suggest that among adults who were previously immunologically naive, few Omicron-wave (BA.1/BA.2) and Delta-wave infections were asymptomatic. Compared with individuals with Delta-wave infections, individuals with Omicron-wave infections were less likely to seek health care and experience postacute symptoms.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Doll reported receiving grants from St Luke’s Wood River Foundation outside the submitted work. Dr Waghmare reported receiving grants from Pfizer, Vir Biotechnology, GSK, Allovir, and Amazon outside the submitted work. Dr Boeckh reported receiving grants from Vir Biotechnology, Merck, Amazon, GSK, Ridgeback, and Regeneron; personal fees from Merck; and consulting for Vir Biotechnology outside the submitted work. Dr Crotty reported receiving personal fees from GSK, Merck, J.P. Morgan Chase, Citi, Morgan Stanley, Avalia NZ, Nutcracker Therapeutics, University of California, California State University, United Airlines, BioNTech, Adagio Therapeutics, Invivyd Therapeutics, and Roche outside the submitted work; in addition, Dr Crotty has a patent for various aspects of T-cell epitope and vaccine design pending. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Prevalence of Acute COVID-19 General Symptoms by Variant
Percentages were estimated among participants who submitted a survey for that day. Only participants experiencing symptoms are included (n = 155).
Figure 2.
Figure 2.. Mean Severity of Acute COVID-19 Symptoms by Variant
Percentages were estimated among participants who submitted a survey for that day. Only participants experiencing symptoms are included (n = 155). EET indicates eyes, ears, and throat; GI, gastrointestinal.
Figure 3.
Figure 3.. Histogram of Distinct Acute Symptoms Reported by Week and Postacute Symptom Status
Only persons who were not vaccinated and had 1 episode of SARS-CoV-2 were included (n = 142).
Figure 4.
Figure 4.. Comparison of Participant Enrollment and End of Study Self-rated Health and Ability Scores
At each time point, participants rated their overall health (range, 1-5; higher score indicates better health), concentration & memory (range, 1-4; higher score indicates better abilities), and ability to walk and climb stairs (range, 1-4; higher score indicates better abilities). Dots represent the proportion of participants by variant and SARS-CoV-2 status whose responses align with a given survey pattern. Areas shaded in orange represent a decline in score at the end of study survey, while shaded blue areas represent a positive score gain at the end of study.
See this image and copyright information in PMC

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